The present invention, in some embodiments thereof, relates to a method of delivering a medicament (e.g., a drug) or a diagnostic agent to a subject and, more particularly, but not exclusively, to an implantable drug delivery device.
Drugs are designed to provide a therapeutic effect on diseased or damaged cell type(s) or tissue(s). However, occasionally, due to lack of cell specificity, limited solubility and/or poor distribution of the drug, high doses of drug molecules are needed to achieve a therapeutic effect on cells of a tissue-of-interest. In spite of being expensive, administering of high drug concentrations may be deleterious to the non-target cells/tissues. For example, treating of small cell lung cancer with systemic administration of chemotherapy drugs (e.g., cisplatin and etoposide) is associated with side effects such as hair loss, sickness (nausea), fatigue, diarrhea, mouth ulcers and anemia. In addition, most drugs and carriers (e.g., polymers, liposomes, emulsions, micro and nanoparticles) have limited capacity of penetrating the blood-brain barrier.
Magnetic resonance imaging (MRI), X-ray imaging including computed tomography (CT) as well as radiography and fluoroscopy, are the most widely used modalities in modern medical imaging. The contrast agents used for CT and MRI include small (e.g., less than 1 kDa) molecular contrast media (SMCM) such as Gd-DTPA [a complex of gadolinium with a chelating agent (diethylenetriamine penta-acetic acid; DTPA)], Gd-DTPA-BMA, Gd-DOTA, diatrizoate, Iohexol, Iopamidol Iodixano, or large macromolecules contrast media (MMCM) with a blood pool, intravascular distribution (see for example, U.S. Patent Application No. 20070248547). For bone scan, radioactive tracers such as technezium and radioactive iodine (I123) are used. However, the exposure of the whole body (e.g., via intravenous administration) to such agents can be associated with undesired side effects (e.g., nausea, dizziness) and can also result in long-term damage to healthy cells (e.g., increase the risk to cancer).
Various means for delivery of a drug to a tissue-of-interest are available. For example, drugs can be administered via a central line (i.e., a tube which is inserted under the skin into a vein above the heart), a catheter (e.g., for abdominal injection of chemotherapy in ovarian cancer), a needle or an implanted drug reservoir with injection means (e.g., a catheter with an infusion or mechanic pump). In addition, the Percutaneous Hepatic Perfusion (PHP) system (Delcath system, NY, USA), composed of catheters and filters, was developed for administering chemotherapy to the liver. It infuses the drug directly to the liver via the hepatic artery, filters the venous effluent from the liver outside of the body and returns the filtered blood to the jugular vein.
Fabrication of nanoscopic and microscopic hollow structures such as polymer tubes receives increasing attention due to the potential application of tubes in drug release.
U.S. Pat. Appl. No. 20060142466 discloses a polymer-carbon nanotube material for drug delivery.
The electrospinning process is well-known for producing nanofibers and polymeric nanofibers in particular (Reneker D H., et al., 2006; Ramakrishna S., et al., 2005; Li D, et al., 2004; PCT WO 2006/106506 to the present inventor).
Methods of fabricating tubes by electrospinning include the TUFT process (Bognitzki et al. 2000) which uses the electrospun nanofibers as templates; the modification of the TUFT process using the sol-gel procedure (Caruso et al., 2001); co-electrospinning of two different solutions to produce core-shell nanofibers (Sun Z, et al., 2003; Yu J H, et al., 2004; Huang Z M, et al., 2006; Jiang H., et al., 2005; Zhang Y Z., et al., 2006) followed by the selective removal of the core (Li D., et al., 2004; Li D., et al., 2005; Zussman E, et al., 2006); and production of hollow fibers by introducing a liquid containing a polymer to a porous template material, and removal of the template following polymer solidification (US patent application No. 20060119015 to Wehrspohn R., et al.).
Studies show that co-electrospinning of two polymeric solutions which are sufficiently viscous, spinnable and immiscible can result in solid core-shell fibers (i.e., filled fibers and not hollow fibers) (Li D., et al., 2006; Loscertales I G., et al., 2002; Loscertales I G., et al., 2004). Sun Z et al. (2003) showed that although core-shell nanofibers made of miscible solutions can be achieved this process is less controllable since mutual diffusion can take place in the Taylor cone and during the jet stretching.
PCT/IB2007/054001 to the present inventor (which is fully incorporated herein by reference) discloses methods of producing electrospun microtubes (i.e., hollow fibers) which can be further filled with liquids and be used as microfluidics.